The Qa and TL cell surface antigens determined by the major histocompatibility complex (MHC) of the mouse possess several unique characteristics that suggest that they may have an important role in immune functioning and/or leukemogenesis. Our goal, therefore, has been to characterize the Qa and TL genes by molecular genetic techniques so that we can study them in more detail. By use of Southern blot techniques, we first identified several restriction fragment length polymorphisms, which are determined by Q and TL subregions of the MHC. Mutant studies were then performed and indicated that one restriction fragment was absent in a Qa-2 mutant strain. Subsequent DNA-mediated gene transfer studies confirmed the identity of this DNA fragment as part of the gene determining a Qa antigen. Additional genetic allelism and polymorphism studies indicate that the gene determining this Qa antigen is relatively nonpolymorphic. These new results point to the possible importance of this gene to the survival and functioning of the organism. (CS)